Calculated Non-HDL Cholesterol Includes Cholesterol in Larger Triglyceride-Rich Lipoproteins in Hypertriglyceridemia

CONTEXT: Calculated non–high-density lipoprotein (HDL) cholesterol (non-HDLC) should selectively include cholesterol from atherogenic lipoproteins to be a reliable risk marker of cardiovascular disease. In hypertriglyceridemia (HTG), there is increased abundance of larger and less atherogenic triglyceride-rich lipoproteins (TRL), namely, larger very-low-density lipoproteins (VLDL), and chylomicrons. OBJECTIVE: We aim to demonstrate that serum triglyceride (TG) level has a substantial impact on non-HDLC’s ability to represent cholesterol from atherogenic lipoproteins, even though TG is not part of the calculation for non-HDLC. DESIGN: Analysis of lipid profile data SETTINGS: Lipid Clinic patient cohort, and Biochemistry Laboratory patient cohort PATIENTS OR OTHER PARTICIPANTS: 7,492 patients in the Lipid Clinic cohort with baseline lipid profiles documented prior to starting lipid-lowering medications and 156,311 lipid profiles from The Ottawa Hospital Biochemistry Laboratory cohort. INTERVENTION: None MAIN OUTCOME MEASURE: Our modeling process includes derivation of TG-interval–specific lipoprotein composition factor (LCF) for TRL, which represents the mass ratio of cholesterol to TG in TRL. A high LCF indicates that the TRLs are mainly the cholesterol-rich atherogenic remnant lipoproteins. A low LCF indicates that the TRLs are mainly the TG-rich larger VLDL and chylomicrons. RESULTS: As serum TG increases, there is progressive decline in the LCF for TRL, which indicates that the calculated non-HDLC level reflects progressive inclusion of cholesterol from larger TRL. This is shown in both cohorts. CONCLUSIONS: Calculated non-HDLC is influenced by TG level. As TG increases, non-HDLC gradually includes more cholesterol from larger TRL, which are less atherogenic than LDL and remnant lipoproteins.